This application requests five years of continued support for a Multi- disciplinary program of research on Mental Retardation and Developmental Psychopathology. The Program emphasizes the interaction of neuromaturational genetic, and environmental factors in the emergence, course of specific syndromes as well as the development of individuals with mental retardation and developmental disorders. The program is unified by shared theoretical perspectives, methods, and research strategies. Processes are studied at various levels, including genetic, molecular, brain functioning, neuropsychology, clinical symptomatology, and adaptation and competence of retarded individuals as whole people. A particular concern is the interaction of neurobiological and neuropsychological factors in the understanding and aspects of competence as well as disability. The research Project areas focus on major domains of theoretical and clinical importance in relation to understanding of mental retardation and developmental disorders. Regulation of arousal and attention to conditions of environmental and biological risk, Interaction of genetic and biological factors in the pathogenesis of Tourette's syndrome and associated disorders, Autism and Asperger Syndrome-neurocognitive studies of social development and Neurobiological and developmental processes in genetic forms of mental retardation: Williams, Prader-Willi, and autism. The Program Project includes a range of specific syndromes and disorders, including autism, Asperger, Tourette's Syndrome, Obsessive-compulsive disorder, Attention Deficit Hyperactivity Disorder, Prader-Willi, and Williams syndromes, as well as children with developmental difficulties related to exposure to drugs and psychosocial adversity. These conditions are studied as important in their own right as clinical conditions and also as models for studying gene-environment interaction, developmental mechanisms, and developmental process over the course of life. Neuropsychological, behavioral, genetic, brain-function, developmental and other findings an be compared across the various diagnostic groups, to clarify basic mechanisms (such as the development of social competence) and clinical correlates (such as arousal/attentional or obsessive-compulsive symptomatology). The Program is also supported by Core Research Resources: Assessment and Biostatistics and Methodology. These core resources provide state-of-the-art collaboration and consultation for all of the Project Areas.